Ricardo Costa, MD, MSC, a medical oncologist in the Department of Breast Oncology at Moffitt Cancer Center, discusses the implications of the phase 3 KEYNOTE-522 trial (NCT03036488) trial in patients with high-risk, early-stage triple-negative breast cancer (TNBC). 

the FDA approved pembrolizumab (Keytruda) for the treatment of this patient population when combined with chemotherapy

 in the neoadjuvant setting, followed by single-agent adjuvant treatment after surgery, based on data from KEYNOTE-522.

The phase 3 trial randomly assigned 1174 patients in a 2:1 fashion to receive neoadjuvant chemotherapy with or without pembrolizumab. The trial enrolled patients with both node-negative and -positive disease, and tumor stage ranged from T1c N1/N2 to T2 to T4 and N0 to N2, per AJCC criteria.

The practice-changing results of KEYNOTE-522 made neoadjuvant pembrolizumab plus chemotherapy and adjuvant pembrolizumab monotherapy one of the standard options for patients with high-risk, early-stage TNBC, Costa starts. This includes patients with a T2 tumor or an N1-positive breast cancer at presentation, which are subsets of disease associated with a higher chance of cancer recurrence compared with other histologies such as estrogen receptor–positive breast cancer, Costa explains.

The trial met its 2 primary end points for pathologic complete response (pCR) and event-free survival (EFS). Patients treated in the pembrolizumab arm achieved a pCR rate of 64.8%, compared with 51.2% for patients in the placebo arm. Those in the pembrolizumab arm also achieved an estimated 3-year EFS rate of 84.5%, compared with 76.8% for those in the placebo arm.

These data suggested that pembrolizumab adds to the probability of shrinking the tumor and eliminating its invasive component, and the addition of pembrolizumab was associated with a higher chance of EFS, Costa continues. Based on a stratified analysis of PD-L1 expression, PD-L1 is prognostic, but not predictive, of benefit, Costa adds. This means that it is not necessary to check for PD-L1 expression prior to recommending pembrolizumab combined with chemotherapy in this high-risk patient population, Costa concludes.

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Ricardo Costa, MD, MSC, discusses the implications of the phase 3 KEYNOTE-522 trial trial in patients with high-risk, early-stage triple-negative breast cancer.  

Dr. Costa on the Implications of the KEYNOTE-522 Trial in TNBC

Ricardo Costa, MD, MSC, a medical oncologist in thhe Department of Breast Oncology at Moffitt Cancer Center, discusses the use of neoadjuvant pembrolizumab (Keytruda) plus chemotherapy, followed by adjuvant pembrolizumab monotherapy, in patients with high-risk, early-stage triple-negative breast cancer (TNBC).

the FDA approved pembrolizumab for the treatment of patients with high-risk, early-stage TNBC

in combination with chemotherapy as neoadjuvant treatment, followed by a single-agent adjuvant treatment after surgery, based on data from the phase 3 KEYNOTE-522 trial (NCT03036488).

The phase 3 trial randomly assigned 1174 patients in a 2:1 fashion to receive neoadjuvant chemotherapy with or without pembrolizumab. Chemotherapy consisted of 4 cycles of carboplatin plus paclitaxel, which was followed by 4 cycles of doxorubicin or epirubicin plus cyclophosphamide. Those in the pembrolizumab arm continued with pembrolizumab monotherapy after surgery for 9 cycles, or until patients experienced progression or unacceptable toxicity. The trial enrolled patients with both node-negative and -positive disease. Tumor stage ranged from T1c N1/N2 to T2 to T4 and N0 to N2, per AJCC criteria.

In a previously reported data on the trial’s co-primary end points, the pathological complete response rate was 64.8% for patients treated in the pembrolizumab arm, compared with 51.2% for those in the chemotherapy alone arm.

Additionally, the estimated 3-year event-free survival was 84.5% in those treated with pembrolizumab plus chemotherapy, compared with 76.8% for those treated with chemotherapy alone. At a median follow-up of 39.0 months, the pembrolizumab regimen resulted in a 37% reduction in the risk of disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer, or death from any cause (HR, 0.63; 95% CI, 0.48-0.82; 

These data continue to support the use of neoadjuvant pembrolizumab plus chemotherapy, followed by adjuvant pembrolizumab, for patients with high-risk, early-stage TNBC, Costa concludes.

Ricardo Costa, MD, MSC, discusses the use of neoadjuvant pembrolizumab plus chemotherapy, followed by adjuvant pembrolizumab monotherapy, in patients with high-risk, early-stage triple-negative breast cancer.

Dr. Costa on the Efficacy of Neoadjuvant Pembrolizumab Plus Chemotherapy in Early-Stage TNBC

Ricardo Costa, MD, MSc, medical oncologist, Department of Breast Oncology, Clinical Investigator Track, Moffitt Cancer Center, discusses the patient population included in the phase 3 OlympiA trial (NCT02032823) in breast cancer.

Findings from the randomized OlympiA trial demonstrated a statistically meaningful improvement in disease-free survival with adjuvant olaparib (Lynparza) vs placebo in patients with 

2-mutant, HER2-negative, early-stage breast cancer. The large, multinational trial enrolled over 800 patients with germline pathogenic or likely pathogenic 

 mutations. Patients were randomized 1:1 to treatment with one year of adjuvant olaparib or placebo, Costa says. 

Inclusion criteria for OlympiA stated that patients needed have a diagnosis of HER2–negative disease, Costa adds. Moreover, the majority of patients enrolled on the study had triple-negative breast cancer, Costa concludes.

Ricardo Costa, MD, MSc, discusses the patient population included in the phase 3 OlympiA trial in breast cancer. 


Dr. Costa on the Patients Included in the OlympiA Trial in HER2- Breast Cancer 

Ricardo Costa, MD, MSc, medical oncologist, Department of Breast Oncology, Clinical Investigator Track, Moffitt Cancer Center, discusses ongoing research efforts in triple-negative breast cancer (TNBC).

Although drug development has not moved as rapidly in TNBC as it has in HER2-positive breast cancer, significant research efforts are underway for patients with TNBC, Costa says. Notably, immunotherapy remains an area of research to improve anticancer activity without compromising safety in this patient population, Costa explains. Moreover, immunotherapy could minimize the use of chemotherapy in TNBC, Costa adds. 

Additionally, investigational antibody-drug conjugates (ADCs) are in clinical development, Costa says. These agents could offer an alternative option to the ADC sacituzumab govitecan-hziy (Trodelvy), which received a full approval on April 7, 2021, by the FDA for the treatment of patients with unresectable locally advanced or metastatic TNBC who have received at least 2 prior systemic therapies, including one for metastatic disease. 

Additionally, PARP inhibitors could play a significant role in the adjuvant treatment of patients with TNBC who harbor germline 

Ricardo Costa, MD, MSc, discusses ongoing research efforts in triple-negative breast cancer.



Ricardo Costa, MD, MSc

Articles

Dr. Costa on the Implications of the KEYNOTE-522 Trial in TNBC

Dr. Costa on the Efficacy of Neoadjuvant Pembrolizumab Plus Chemotherapy in Early-Stage TNBC

Dr. Costa on the Patients Included in the OlympiA Trial in HER2- Breast Cancer

Dr. Costa Discusses Ongoing Research Efforts in TNBC